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Journal of Dairy Science Apr 2020Service sire has been recognized as an important factor affecting dairy herd fertility. Our group has reported promising results on gene mapping and genomic prediction...
Service sire has been recognized as an important factor affecting dairy herd fertility. Our group has reported promising results on gene mapping and genomic prediction of dairy bull fertility using autosomal SNP markers. Little is known, however, about the genetic contribution of sex chromosomes, which are enriched in genes related to sexual development and reproduction. As such, the main goal of this study was to investigate the effect of SNP markers on X and Y chromosomes (BTAX and BTAY, respectively) on sire conception rate (SCR) in US Holstein bulls. The analysis included a total of 5,014 bulls with SCR records and genotypes for roughly 291k SNP located on the autosomes, 1.5k SNP located on the pseudoautosomal region (PAR), 13.7k BTAX-specific SNP, and 24 BTAY-specific SNP. We first performed genomic scans of the sex chromosomes, and then we evaluated the genomic prediction of SCR including BTAX SNP markers in the predictive models. Two markers located on PAR and 3 markers located on the X-specific region showed significant associations with sire fertility. Interestingly, these regions harbor genes, such as FAM9B, TBL1X, and PIH1D3, that are directly implicated in testosterone concentration, spermatogenesis, and sperm motility. On the other hand, BTAY showed very low genetic variability, and none of the segregating markers were associated with SCR. Notably, model predictive ability was largely improved by including BTAX markers. Indeed, the combination of autosomal with BTAX SNP delivered predictive correlations around 0.343, representing an increase in accuracy of about 7.5% compared with the standard whole autosomal genome approach. Overall, this study provides evidence of the importance of both PAR and X-specific regions in male fertility in dairy cattle. These findings may help to improve conception rates in dairy herds through accurate genome-guided decisions on bull fertility.
Topics: Animals; Cattle; Chromosome Mapping; Female; Fertility; Fertilization; Genetic Markers; Genome; Genotype; Male; Polymorphism, Single Nucleotide; Pseudoautosomal Regions; Sex Chromosomes; Sperm Motility; Spermatogenesis
PubMed: 32063375
DOI: 10.3168/jds.2019-17767 -
Genes Nov 2021We present a detailed molecular cytogenetic analysis of a reciprocal translocation between horse (ECA) chromosomes Y and 13 in a Friesian stallion with complete meiotic...
We present a detailed molecular cytogenetic analysis of a reciprocal translocation between horse (ECA) chromosomes Y and 13 in a Friesian stallion with complete meiotic arrest and azoospermia. We use dual-color fluorescence in situ hybridization with select ECAY and ECA13 markers and show that the translocation breakpoint in ECAY is in the multicopy region and in ECA13, at the centromere. One resulting derivative chromosome, Y;13p, comprises of ECAY heterochromatin ( array), a small single copy and partial Y multicopy region, and ECA13p. Another derivative chromosome 13q;Y comprises of ECA13q and most of the single copy ECAY, the pseudoautosomal region and a small part of the Y multicopy region. A copy number (CN) analysis of select ECAY multicopy genes shows that the Friesian stallion has significantly ( < 0.05) reduced CNs of and , suggesting that the translocation may not be completely balanced, and genetic material is lost. We discuss likely meiotic behavior of abnormal chromosomes and theorize about the possible effect of the aberration on Y regulation and the progression of meiosis. The study adds a unique case to equine clinical cytogenetics and contributes to understanding the role of the Y chromosome in male meiosis.
Topics: Animals; Centromere; Cytogenetic Analysis; Cytogenetics; DNA Copy Number Variations; Heterochromatin; Horses; Male; Meiosis; Translocation, Genetic; Y Chromosome
PubMed: 34946841
DOI: 10.3390/genes12121892 -
Nature Sep 2020After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single...
After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist. Here we present a human genome assembly that surpasses the continuity of GRCh38, along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome, we reconstructed the centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis ampliconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes.
Topics: Centromere; Chromosomes, Human, X; CpG Islands; DNA Methylation; DNA, Satellite; Female; Genome, Human; Humans; Hydatidiform Mole; Male; Pregnancy; Reproducibility of Results; Telomere; Testis
PubMed: 32663838
DOI: 10.1038/s41586-020-2547-7 -
Genetics Jun 2019Faithful segregation of homologous chromosomes at meiosis requires pairing and recombination. In taxa with dimorphic sex chromosomes, pairing between them in the...
Faithful segregation of homologous chromosomes at meiosis requires pairing and recombination. In taxa with dimorphic sex chromosomes, pairing between them in the heterogametic sex is limited to a narrow interval of residual sequence homology known as the pseudoautosomal region (PAR). Failure to form the obligate crossover in the PAR is associated with male infertility in house mice () and humans. Yet despite this apparent functional constraint, the boundary and organization of the PAR is highly variable in mammals, and even between subspecies of mice. Here, we estimate the genetic map in a previously documented expansion of the PAR in the subspecies and show that the local recombination rate is 100-fold higher than the autosomal background. We identify an independent shift in the PAR boundary in the subspecies and show that it involves a complex rearrangement, but still recombines in heterozygous males. Finally, we demonstrate pervasive copy-number variation at the PAR boundary in wild populations of , , and Our results suggest that the intensity of recombination activity in the PAR, coupled with relatively weak constraints on its sequence, permit the generation and maintenance of unusual levels of polymorphism in the population of unknown functional significance.
Topics: Animals; Chromosome Mapping; Evolution, Molecular; Female; Male; Meiosis; Mice; Pseudoautosomal Regions; Recombination, Genetic; Species Specificity; X Chromosome; Y Chromosome
PubMed: 31028113
DOI: 10.1534/genetics.119.302232 -
Frontiers in Cell and Developmental... 2021During meiotic prophase I, X and Y chromosomes in mammalian spermatocytes only stably pair at a small homologous region called the pseudoautosomal region (PAR). However,... (Review)
Review
During meiotic prophase I, X and Y chromosomes in mammalian spermatocytes only stably pair at a small homologous region called the pseudoautosomal region (PAR). However, the rest of the sex chromosomes remain largely unsynapsed. The extensive asynapsis triggers transcriptional silencing - meiotic sex chromosome inactivation (MSCI). Along with MSCI, a special nuclear territory, sex body or XY body, forms. In the early steps of MSCI, DNA damage response (DDR) factors, such as BRCA1, ATR, and γH2AX, function as sensors and effectors of the silencing signals. Downstream canonical repressive histone modifications, including methylation, acetylation, ubiquitylation, and SUMOylation, are responsible for the transcriptional repression of the sex chromosomes. Nevertheless, mechanisms of the sex-body formation remain unclear. Liquid-liquid phase separation (LLPS) may drive the formation of several chromatin subcompartments, such as pericentric heterochromatin, nucleoli, inactive X chromosomes. Although several proteins involved in phase separation are found in the sex bodies, when and whether these proteins exert functions in the sex-body formation and MSCI is still unknown. Here, we reviewed recent publications on the mechanisms of MSCI and LLPS, pointed out the potential link between LLPS and the formation of sex bodies, and discussed its implications for future research.
PubMed: 34485277
DOI: 10.3389/fcell.2021.674203 -
Frontiers in Molecular Neuroscience 2022The neural cell adhesion protein neuroligin-4 has puzzled neuroscientists and geneticist alike for almost two decades. Its clinical association with autism spectrum...
The neural cell adhesion protein neuroligin-4 has puzzled neuroscientists and geneticist alike for almost two decades. Its clinical association with autism spectrum disorders (ASD) is well established, however, its diversification into sex chromosome-specific copies, and , remains uncharted territory. Just recently, the presence of substantial neuroligin-4 sequence differences between humans and laboratory mice, in which is a pseudoautosomal gene, could be explained as a consequence of dramatic changes affecting the pseudoautosomal region on both sex chromosomes in a subset of rodents, the clade eumuroida. In this study, we describe the presence of sex chromosome-specific copies of neuroligin-4 genes in the Mongolian gerbil () marking the first encounter of its kind in rodents. Gerbils are members of the family Muridae and are closely related to mice and rats. Our results have been incorporated into an extended evolutionary analysis covering primates, rodents, lagomorphs, treeshrews and culogos comprising together the mammalian superorder euarchontoglires. We gathered evidence that substantial changes in neuroligin-4 genes have also occurred outside eumuroida in other rodent species as well as in lagomorphs. These changes feature, e.g., a general reduction of its gene size, an increase in its average GC-content as well as in the third position (GC3) of synonymous codons, and the accumulation of repetitive sequences in line with previous observations. We further show conclusively that the diversification of neuroligin-4 in sex chromosome-specific copies has happened multiple times independently during mammal evolution proving that Y-chromosomal genes do not originate from a single common ancestor.
PubMed: 35431802
DOI: 10.3389/fnmol.2022.838262 -
Vox Sanguinis Oct 2022The Xg blood group is composed of two antigens, Xg (XG1) and CD99 (XG2 and MIC2). The XG and CD99 are homologous genes located on pseudoautosomal region 1 of the X and Y...
BACKGROUND AND OBJECTIVES
The Xg blood group is composed of two antigens, Xg (XG1) and CD99 (XG2 and MIC2). The XG and CD99 are homologous genes located on pseudoautosomal region 1 of the X and Y chromosomes. The expressions of Xg and CD99 are co-regulated by a single nucleotide polymorphism (rs311103) in the GATA-1 binding region. Another mechanism of the Xg(a-) phenotype is the genomic deletion of approximately 114 kb, including the XG gene. Anti-Xg seems to be naturally occurring by detection in males who have never been transfused.
MATERIALS AND METHODS
In this study, we identified 23 anti-Xg producers among 580,115 donors (0.004%). Additional 12 anti-Xg producers were also identified from a separate cohort.
RESULTS
All 35 anti-Xg producers were male. Genomic DNA was obtained from 34 of 35 producers, and all 34 producers were confirmed to carry the XG-gene-deficient allele (XGdel). The breakpoints of all 34 producers were identical. The XGdel was also identified in 12 non-producers of anti-Xg among 860 donors who have no antibodies against RBCs, and the breakpoints were also identical with the anti-Xg producers.
CONCLUSION
Our results will serve as the basis for a more complete understanding of Xg blood group polymorphisms.
Topics: Blood Donors; Blood Group Antigens; Female; Genetic Background; Humans; Japan; Male; Phenotype
PubMed: 36102098
DOI: 10.1111/vox.13342 -
Placenta May 2024Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal...
INTRODUCTION
Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes.
OBJECTIVES
We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation.
STUDY DESIGN
We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences.
RESULTS
Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3.
DISCUSSION
This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes.
Topics: Humans; Female; Pregnancy; Male; Placenta; Sex Characteristics; High-Throughput Nucleotide Sequencing; RNA, Messenger; Adult; Transcriptome; Pregnancy Trimester, Third; Sequence Analysis, RNA; Pregnancy Trimester, First
PubMed: 38537412
DOI: 10.1016/j.placenta.2024.03.005 -
Cells Mar 2022The conspicuous colour sexual dimorphism of guppies has made them paradigmatic study objects for sex-linked traits and sex chromosome evolution. Both the X- and...
The conspicuous colour sexual dimorphism of guppies has made them paradigmatic study objects for sex-linked traits and sex chromosome evolution. Both the X- and Y-chromosomes of the common guppy () are genetically active and homomorphic, with a large homologous part and a small sex specific region. This feature is considered to emulate the initial stage of sex chromosome evolution. A similar situation has been documented in the related Endler's and Oropuche guppies () indicating a common origin of the Y in this group. A recent molecular study in the swamp guppy () reported a low SNP density on the Y, indicating Y-chromosome deterioration. We performed a series of cytological studies on to show that the Y-chromosome is quite small compared to the X and has accumulated a high content of heterochromatin. Furthermore, the Y-chromosome stands out in displaying CpG clusters around the centromeric region. These cytological findings evidently illustrate that the Y-chromosome in is indeed highly degenerated. Immunostaining for SYCP3 and MLH1 in pachytene meiocytes revealed that a substantial part of the Y remains associated with the X. A specific MLH1 hotspot site was persistently marked at the distal end of the associated XY structure. These results unveil a landmark of a recombining pseudoautosomal region on the otherwise strongly degenerated Y chromosome of . Hormone treatments of females revealed that, unexpectedly, no sexually antagonistic color gene is Y-linked in . All these differences to the group of guppies indicate that the trajectories associated with the evolution of sex chromosomes are not in parallel.
Topics: Animals; Cyprinodontiformes; Female; Male; Poecilia; Sex Chromosomes; Wetlands; Y Chromosome
PubMed: 35406682
DOI: 10.3390/cells11071118 -
Chromosoma Aug 2014Sex chromosomes differ from autosomes by dissimilar gene content and, at a more advanced stage of their evolution, also in structure and size. This is driven by the...
Sex chromosomes differ from autosomes by dissimilar gene content and, at a more advanced stage of their evolution, also in structure and size. This is driven by the divergence of the Y or W from their counterparts, X and Z, due to reduced recombination and the resulting degeneration as well as the accumulation of sex-specific and sexually antagonistic genes. A paradigmatic example for Y-chromosome evolution is found in guppies. In these fishes, conflicting data exist for a morphological and molecular differentiation of sex chromosomes. Using molecular probes and the previously established linkage map, we performed a cytogenetic analysis of sex chromosomes. We show that the Y chromosome has a very large pseudoautosomal region, which is followed by a heterochromatin block (HCY) separating the subtelomeric male-specific region from the rest of the chromosome. Interestingly, the size of the HCY is highly variable between individuals from different population. The largest HCY was found in one population of Poecilia wingei, making the Y almost double the size of the X and the largest chromosome of the complement. Comparative analysis revealed that the Y chromosomes of different guppy species are homologous and share the same structure and organization. The observed size differences are explained by an expansion of the HCY, which is due to increased amounts of repetitive DNA. In one population, we observed also a polymorphism of the X chromosome. We suggest that sex chromosome-linked color patterns and other sexually selected genes are important for maintaining the observed structural polymorphism of sex chromosomes.
Topics: Animals; Chromosome Banding; DNA Fingerprinting; Female; Indoles; Karyotyping; Male; Meiosis; Metaphase; Poecilia; Polymorphism, Genetic; X Chromosome; Y Chromosome
PubMed: 24676866
DOI: 10.1007/s00412-014-0455-z